Iatrogenic Complications of Steroid Therapy

Question 1

What are the peaks of cortisol in the diurnal rhythm related to?

Answer 1

food intake

Question 2

What enzyme converts cortisol to cortisone in the kidney?

Answer 2

11 beta HSD 2

Question 3

What enzyme converts cotisone to cortisol in the liver?

Answer 3

11 beta HSD 1

Question 4

Why doesn’t cortisol activate the mineralocorticoid receptors as much as it should based on its high affinity for the receptor?

Answer 4

the receptor is colocalised with the enzyme 11 beta HSD 1 to convert it to cortisone which has low affinity for the mineralocorticoid receptor

Question 5

What are the side effects of cortisol/cortisone treatment for Addison’s?

Answer 5

none as long as the treatment is well managed but if overdose can get Cushing’s symptoms

Question 6

What are some of the iatrogenic complications of glucocorticoid therapy?

Answer 6

Cushing’s syndrome, adrenal suppression, immunosuppresion, peptic ulcers, osteoporosis, inhibition of linear growth in children

Question 7

What may be a consequence of immunosuppression in glucocorticoid therapy?

Answer 7

reactivate latent TB

Question 8

How do glucocorticoids suppress the immune system?

Answer 8

they inhibit mediators of inflammation (eicosanoids, PAF, serotonin, bradykinin) and inhibit the production of inflammatory cytokines

Question 9

What are dissociated steroids and why are they useful?

Answer 9

dissociated steroids targets either the transactivation action or transrepression action of steroids to get the desired effect or avoid certain side effects

Question 10

What is adrenal suppression and how can it be avoided?

Answer 10

adrenal suppression is where the adrenals stop functioning because the high levels of synthetic cortisol in the system negatively feedsback - it can be reduced with a strict dosing regimen, avoiding long lasting drugs, alternating day doses, morning doses and using drugs with reduced absorption - and most importantly by slowly reducing glucocorticoid medication

Question 11

Why does ciclesonide have reduced systemic effects?

Answer 11

it is an inhaled steroid for asthma so goes directly to the lungs, remains dissolved in cell membranes so doesnt enter the blood and has low oral bioavailability so any that is swallowed wont enter the circulation

Question 12

How do glucocorticoids cause osteoporosis?

Answer 12

glucocorticoids inhibit OPG and stimulate RANKL which leads to osteoclast maturation which leads to bone resoprtion